Radon exposure is known to be the second most frequent cause followed by tobacco exposure for lung cancer development. In lung cancer development, microRNAs (miRNAs) play an important role in regulating various target genes associated with this disease. It is well-established that apoptosis is involved in the elimination of cancer cells. However, the mechanisms underlying chronic radon exposure induced miRNAs regulation attributed to result in carcinogenesis and subsequent activation of apoptosis is not completely understood. The aim of this study was thus to examine chronic low level radon exposure on lung miRNAs as a model for carcinogenesis induction and subsequent activation of apoptosis using human bronchial epithelial BEAS-2B cells. Quantitative real-time PCR (qRT-PCR) and flow cytometry were used to determine the miR-34a gene expression and apoptotic rate in BEAS-2B cells. Data demonstrated that chronic radon exposure up-regulated the expressions of miR-34a and enhanced cellular apoptosis in a time-dependent manner. Western blot analysis demonstrated that overexpression of the gene miR-34a enhanced apoptotic rate and elevated proapoptotic Bax protein expression accompanied by decreased protein expressions of antiapoptotic Bcl-2 and PARP-1. It is noteworthy that the apoptotic rate was elevated in BEAS-2B cells transfected with mi-R34a mimic but reduced in mi-R34a inhibitor-transfected cells. Evidence thus indicates that chronic exposure to radon produced up-regulation of miR-34a gene which subsequently enhanced apoptosis in BEAS-2B cells. The observed consequences following chronic radon exposure leading to carcinogenesis appear to involve activation of miR-34a gene.

中文翻译：

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on对miR-34a诱导的人支气管上皮BEAS-2B细胞凋亡的影响。

lung暴露是肺癌发展的第二大原因，其次是烟草暴露。在肺癌的发展中，microRNA（miRNA）在调节与此疾病相关的各种靶基因中起着重要作用。众所周知，凋亡与癌细胞的消除有关。然而，慢性chronic暴露引起的miRNAs调控的机制可能归因于致癌作用和随后的细胞凋亡激活，对此尚未完全了解。因此，本研究的目的是检查肺miRNA上长期低水平的ra暴露，以作为使用人支气管上皮BEAS-2B细胞诱导癌变和随后激活细胞凋亡的模型。实时定量PCR（qRT-PCR）和流式细胞仪用于确定miR-34a基因表达和BEAS-2B细胞凋亡率。数据表明，长期ra暴露以时间依赖性方式上调了miR-34a的表达并增强了细胞凋亡。蛋白质印迹分析表明，miR-34a基因的过表达提高了细胞凋亡率，提高了凋亡前Bax蛋白的表达，同时降低了抗凋亡Bcl-2和PARP-1的蛋白表达。值得注意的是，在mi-R34a模拟物转染的BEAS-2B细胞中凋亡率升高，而在mi-R34a抑制剂转染的细胞中凋亡率降低。因此，有证据表明长期暴露于produced会产生miR-34a基因的上调，继而增强BEAS-2B细胞的凋亡。